Transcutaneous immunization is a new approach to needle-free and device-free immunization using a patch to deliver vaccine antigens and potent adjuvants. Topical skin immunization takes advantage of the immunobiology of the skin leading to safe and effective systemic immune responses. The use of the adjuvant LT has been shown to safely augment the immune response in the context of the skin in both preclinical and clinical settings. This phase I SBIR proposal will focus on the development of a dry self-adhesive flu vaccine patch, which can be manufactured (cGMP) and is practical to apply in the clinic. A dry adhesive patch has been shown to effectively and safely deliver LT in clinical settings. The specific aims of this proposal are to assess the biological activity and potency of LT when formulated with the flu vaccine in adhesive blends containing both LT and trivalent split virus vaccine; to characterize the in vitro release and recovery of influenza vaccine and LT from formulated dried patches; to characterize the systemic and pulmonary mucosal immune responses elicited by topical administered influenza vaccine compared to immune responses elicited by intramuscular injection in preclinical studies; to develop a pilot scale (lot size >1,000 patches) manufacturing process for cGMP production of influenza/LT patches that could support clinical trials. These activities will prepare the groundwork for clinical evaluation of an influenza patch. An average influenza season in the United States is currently associated with 25-30 million flu cases, 150,000 hospitalizations and 20,000 to 40,000 deaths each year. Rates of infection are highest among children, but the most serious illness and influenza related deaths are among the elderly = or >=65 years. Approximately 60% of flu-related hospitalizations occur among the elderly and greater than 90% of flu related deaths are elderly. The effectiveness of inactivated influenza vaccine is dependant upon the age and immune competence of the recipient and the degree of similarity between the viruses and the vaccine in circulation each season. It is well established that the elderly often do not develop protective level of HAl antibodies post-immunization. The safe use of potent adjuvants in the context of the skin may address the relative immune deficit in the elderly and this may be the first target of future clinical evaluation. Needle-free may also aid in the extension of use of a flu patch into the pediatric population where influenza immunization is now recommended by the ACIP and will be a subsequent goal of this development program.